Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL-/- mice

Nat Immunol. 2003 Mar;4(3):255-60. doi: 10.1038/ni894. Epub 2003 Feb 10.


TRAIL, the tumor necrosis factor-related apoptosis-inducing ligand, selectively induces apoptosis of tumor cells, but not most normal cells. Its role in normal, nontransformed tissues is not clear. We report here that mice deficient in TRAIL have a severe defect in thymocyte apoptosis-thus, thymic deletion induced by T cell receptor ligation is severely impaired. TRAIL-deficient mice are also hypersensitive to collagen-induced arthritis and streptozotocin-induced diabetes and develop heightened autoimmune responses. Thus, TRAIL mediates thymocyte apoptosis and is important in the induction of autoimmune diseases.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / pathology
  • Cell Differentiation / physiology
  • Clonal Deletion / immunology
  • Collagen / immunology
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Ovalbumin
  • T-Lymphocytes / pathology
  • T-Lymphocytes / physiology*
  • TNF-Related Apoptosis-Inducing Ligand
  • Thymus Gland / immunology
  • Thymus Gland / pathology
  • Tumor Necrosis Factor-alpha / genetics*


  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Ovalbumin
  • Collagen